Abstract 734P
Background
HLRCC is an autosomal dominant condition due to fumarate hydratase gene (FH) germline pathogenic variants. It is characterized by predisposition to skin and uterine leiomyomas, renal cysts (RCy) and renal cell cancer (RCC). So far, no phenotype/genotype correlations have been described. We aimed to characterize the genetic, clinical, epidemiological and pathological features of RCy and RCC in the largest Spanish series of FH variants carriers.
Methods
We performed a multicentre, observational, retrospective study of a cohort of 197 patients, 74 index, with genetic diagnosis of HLRCC. We analysed FH pathogenic variants, presence of RCy and RCC, diagnosis age, histology, stage, treatment, survival and known risk factors for RCC as arterial hypertension, tobacco exposure and obesity using the software R v3.6.0. The study was approved by the Hospital General Universitario de Elche Ethics Committee.
Results
We identified 27 FH pathogenic variants: 13 missense, 5 frameshift, 4 large deletions, 3 splice site, 2 nonsense. Of 153 patients with radiological records 57 presented RCy (37.3%), which were more frequent in missense variants carriers (p = 0.017). Tobacco exposure (p= 0.076), and obesity (p = 0.058) show a trend to RCy. There were 19 cases of RCC (10.9%) among 175 patients with confirmed clinical information, 11 males/8 females, 7 with RCy. The median age at diagnosis was 37 years, range 10-67. One patient presented 2 synchronous bilateral RCC. Histological patterns were 14 papillary (10 type 2), 4 clear cells, 2 unclassified carcinoma. No significant differences were found by type of variant or risk factors. Six were stage I, 2 stage II, 3 stage III, 4 stage IV, and 4 not available. The median overall survival (mOS) in stages III-IV was 2.9 years [CI 95% 2.4-3.4]. In stages I-II the mOS is not reached. Six patients with metastatic disease received anti-angiogenic treatments with mOS 34.9 months [CI 95%: 29.0-40.9].
Conclusions
RCy were more frequent in missense mutations carriers. The RCC frequency (10.9%) was lower than in other published cohorts. Being papillary type-2 the most frequent histology, other histological patterns do not exclude HLRCC. Anti-angiogenic treatment offered similar results of overall survival than in sporadic RCC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.